1. Field of the Invention
This invention relates to novel imidazole derivatives. More particularly, this invention relates to N-(.omega.-substituted alkyl-phenylalkyl), N-(.omega.-substituted alkylphenyl) and N-(nucleus substituted phenylalkyl) imidazoles possessing an extremely strong inhibitory action for thromboxane synthetase and inhibiting the biosynthesis of thromoboxane A.sub.2.
2. Description of the Prior Art
Up to now, of the compounds having an imidazole skeleton, it has been reported that imidazole, 1-alkylimidazoles, 1-benzylimidazole, 1-(2-isopropylphenyl)imidazole and their analogue possess an inhibitory action for thromboxane synthetase [Prostaglandins, Vol. 13, No. 4, 611-, (1977), BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol. 80, No. 1, 236- (1978)]. However, since imidazole and 1-lower alkylimidazoles of those compounds above show only very weak inhibitory effect, these compounds are hardly applicable as practically effective medicines. On the other hand, 1-benzylimidazole, 1-(2-isopropylphenyl)imidazole, 1-higher alkylimidazoles such as 1-nonylimidazole and 1-decylimidazole, and their analogue show a strong inhibitory effect compared with imidazole and 1-lower alkylimidazoles, but the inhibitory potency of these compounds is yet far from satisfactory one as therapeutically active agents. And the action of these compounds is not a specific inhibitory action for thromboxane synthetase because of possessing both inhibitory actions for thromboxane synthetase and cyclooxygenase. Furthermore, in the case of 1-(2-isopropylphenyl)imidazole, it is difficult to prepare this compound, so that the problem of industrial application remains still unsettled.
Meanwhile, many compounds which have an imidazole skeleton and which might be considered superficially to be similar to the compounds of this invention from a chemical structural standpoint have been reported, e.g., in Monatsch Chem. Vol. 108, No. 5, 1059-, (1977), J. Med. Chem. Vol. 18, No. 8, 833-, (1975), J. Amer. Chem. Soc. Vol. 79, 4922-, (1957), U.S. Pat. No. 3,541,109, French Pat. No. 7,779M, French Pat. No. 1,486,817, Chemical Abstracts, Vol. 71, 90645g, (1969), 83, 164069u, (1975), 88, 36814z, (1978), J. Org. Chem. Vol. 22, 1323-, (1975) British Pat. No. 1,148,103, etc. Although some of these compounds, especially 1-(6-methoxycarbonylhexyl) imidazole, show a inhibitory effect on thromboxane synthetase, but the inhibitory potency is not completely satisfactory as a practical medication, and the others do not show a inhibitory effect on thromboxane synthetase.
Therefore, research directed towards developing compounds possessing a much stronger and more specific inhibitory effect on thromboxane synthetase has been long demanded in the medical field.
As a result of extensive research and experimentation carried out for imidazole derivatives, it was found that such demand was satisfied with use of N-(.omega.-substituted alkylphenylalkyl), N-(.omega.-substituted alkylphenyl) and N-(nucleus-substituted phenylalkyl)imidazole.
The imidazole derivatives of this invention possess a strong and specific inhibitory effect on thromboxane synthetase and are useful as therapeutically active agents for the treatment of inflammation, hypertension, thrombus, cerebral apoplexy and asthma.